title: Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury.
abstract: Secondary degeneration after spinal cord injury (SCI) is caused by increased vascular permeability, infiltration of inflammatory cells, and subsequent focal edema. Therapeutic interventions using neurotrophic factors have focused on the prevention of such reactions to reduce cell death and promote tissue regeneration. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. However, the effect of VEGF on SCI remains controversial. VEGF signaling is primarily regulated through two primary receptors, VEGF receptor 1 (VEGF-R1) and VEGF receptor 2 (VEGF-R2). The purpose of this study was to examine the effects of intraperitoneal administration of VEGF-R1- and VEGF-R2-neutralizing antibodies on a mouse model of SCI. VEGF-R1 blockade, but not VEGF-R2 blockade, decreased the permeability and infiltration of inflammatory cells, and VEGF-R2 blockade caused a significant increase in neuronal apoptosis in the acute phase of SCI. VEGF-R2 blockade decreased the residual tissue area and the number of neural fibers in the chronic phase of SCI. VEGF-R2 blockade worsened the functional recovery and prolonged the latency of motor evoked potentials. These data suggest that endogenous VEGF-R2 plays a crucial role in neuronal protection after SCI.
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Shinozaki
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: masa@a8.keio.jp.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Konomi
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yoshiomi
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Morito
authors.initials: M
authors.lastname: Takano
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Saito
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: hidokano@a2.keio.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology*
chemical_list: D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Functional recovery; Neurotrophic factor; PI3-K; SCI; Spinal cord injury; VEGF; VEGF-R1; VEGF-R2; Vascular endothelial growth factor; Vascular endothelial growth factor receptor; dextran tetramethylrhodamine; dextran-TMR; phosphatidylinositide 3-kinase; spinal cord injury; vascular endothelial growth factor; vascular endothelial growth factor receptor 1; vascular endothelial growth factor receptor 2